Differences in DNA binding properties between E2F1 and E2F4 specify repression of the Mcl-1 promoter

Croxton, Rhonda; Ma, Yihong; Cress, W. Douglas

doi:10.1038/sj.onc.1205232

Cited by 22 publications

(14 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, coexposure to flavopiridol antagonized this process and resulted in a dramatic decrease in mRNA and protein levels. Although these events may reflect the inhibitory effects of flavopiridol on RNA polymerase II, recent studies have shown that the proapoptotic transcription factor E2F1 exerts a negative regulatory effect on Mcl-1 gene expression (34,37) and that this interaction is modulated by flavopiridol (38). The present finding that flavopiridol increased the association of E2F1 with the Mcl-1 promoter is consistent with this notion.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have shown that the Mcl-1 promoter is repressed directly by E2F1 (34,37) and that flavopiridolinduced apoptosis in H1299 lung cancer cells involves a concentration-dependent increase in E2F1 protein levels accompanied by Mcl-1 down-regulation (38). In addition, we previously reported that HDACI/flavopiridol -induced apoptosis in human leukemia cells was associated with disruption of pRb/E2F1 complexes, resulting in increased availability of E2F1 (12).…”

Section: Mcl-1 Expression Is Transcriptionally Regulatedmentioning

confidence: 99%

See 1 more Smart Citation

Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions

Rosato

Almenara

Kolla

et al. 2007

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The mechanism and functional significance of XIAP and Mcl-1 down-regulation in human leukemia cells exposed to the histone deacetylase inhibitor vorinostat and the cyclindependent kinase inhibitor flavopiridol was investigated. Combined exposure of U937 leukemia cells to marginally toxic concentrations of vorinostat and flavopiridol resulted in a marked increase in mitochondrial damage and apoptosis accompanied by pronounced reductions in XIAP and Mcl-1 mRNA and protein. Down-regulation of Mcl-1 and XIAP expression by vorinostat/flavopiridol was associated with enhanced inhibition of phosphorylation of RNA polymerase II and was amplified by caspase-mediated protein degradation. Chromatin immunoprecipitation analysis revealed that XIAP and Mcl-1 down-regulation were also accompanied by both decreased association of nuclear factor-KB (XIAP) and increased E2F1 association (Mcl-1) with their promoter regions, respectively. Ectopic expression of Mcl-1 but not XIAP partially protected cells from flavopiridol/vorinostat -mediated mitochondrial injury at 48 h, but both did not significantly restored clonogenic potential. Flavopiridol/vorinostat -mediated transcriptional repression of XIAP, Mcl-1 -enhanced apoptosis, and loss of clonogenic potential also occurred in primary acute myelogenous leukemia (AML) blasts. Together, these findings indicate that transcriptional repression of XIAP and Mcl-1 by flavopiridol/vorinostat contributes functionally to apoptosis induction at early exposure intervals and raise the possibility that expression levels may be a useful surrogate marker for activity in current trials. [Mol Cancer Ther 2007;6(2):692 -702]

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Mcl-1 Expression Is Transcriptionally Regulatedmentioning

confidence: 99%

Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions

Rosato

Almenara

Kolla

et al. 2007

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Reporter gene assays were carried out as previously described (38). Briefly, cells were cotransfected with a Ϫ203/ ϩ10-Mcl-1-pGL2 plasmid (39) in which firefly luciferase is driven by the Ϫ203 to ϩ10 element of the Mcl-1 gene promoter, or the pGL2-basic empty vector (Promega, Madison, WI) and pRL-TK-luc plasmid encoding for Renilla luciferase. Cells were incubated for 6 h and then treated with BAY 43-9006 for an additional 20 h, after which the activity of firefly and Renilla luciferases was measured using the Dual-Luciferase reporter assay system (Promega).…”

Section: Methodsmentioning

confidence: 99%

Apoptosis Induced by the Kinase Inhibitor BAY 43-9006 in Human Leukemia Cells Involves Down-regulation of Mcl-1 through Inhibition of Translation

Rahmani

Davis

Bauer

et al. 2005

Journal of Biological Chemistry

272

250

View full text Add to dashboard Cite

BAY 43-9006 is a kinase inhibitor that induces apoptosis in a variety of tumor cells. Here we report that treatment with BAY 43-9006 results in marked cytochrome c and AIF release into the cytosol, caspase-9, -8, -7, and -3 activation, and apoptosis in human leukemia cells (U937, Jurkat, and K562). Pronounced apoptosis was also observed in blasts from patients with acute myeloid leukemia. The Ras/Raf/mitogen-activated protein kinase (MEK) 2 /extracellularsignal-regulated kinase (ERK) cascade plays a critical role in relaying signals from cell surface receptors to various cytoplasmic and nuclear proteins involved in diverse biological process such as cell growth, transformation, differentiation, and apoptosis (1). Aberrant activation of this pathway has been implicated in the development of many tumor types, and constitutive activation of this pathway has been observed in ϳ30% of all human cancer. The serine/threonine Raf kinase family, which consists of three proteins, C-Raf (also referred to as Raf-1), B-Raf, and A-Raf, is an essential component of this pathway (1, 2). Strikingly, B-Raf-activating mutations have been observed in ϳ70% of malignant melanomas (3, 4) and at lower frequencies in a number of other human cancer types, including colorectal (3, 5), ovarian, and papillary thyroid carcinomas (3, 6, 7). Moreover, overexpression of constitutively active c-Raf is sufficient to induce transformation of NIH 3T3 cells (8). Increased Raf/MEK/ERK activity has also been observed in a variety of leukemias, including acute myeloid leukemia (AML) and chronic myeloid leukemia (9, 10). In addition, constitutive activation of this pathway diminishes apoptosis in hematopoietic cells (11) and abrogates the cytokine dependence of several human and murine cytokine-dependent hematopoietic cells lines (e.g. TF-1, FDC-P1, and FL5.12) (12). Conversely, inhibition of this pathway by pharmacologic MEK inhibitors such as PD98059 or U0126 enhances apoptosis induction by a variety of agents, including paclitaxel (13) UCN01 (14), STI571 (15), proteasome inhibitors (16), and lovastatin (17). For these reasons, disrupting the Ras/Raf/MEK/ERK pathway represents an attractive anticancer strategy, particularly in leukemia cells.BAY 43-9006, a novel bi-aryl urea, has shown promising preclinical activity against a variety of tumor cell types and is currently undergoing phase II/III clinical evaluation (18 -20). Although it was initially developed as a specific inhibitor of C-Raf and B-Raf, subsequent studies revealed that this compound also inhibits several other important tyrosine kinases involved in tumor progression, including vascular epidermal growth factor receptor-2, vascular epidermal growth factor receptor-3, platelet-derived growth factor receptor-␤, Flt3, and c-Kit (21). Interestingly, BAY 43-9006 has been shown to inhibit C-Raf and wild type as well as mutant V600E B-Raf kinase activities in vitro and to diminish MEK/ERK activation in various tumor cell lines, including those harboring mutant Ras or B-Raf (21-23).Several studies...

show abstract

“…Electrophoretic mobility shift assays (EMSA) were done essentially as described (24,25). DNA oligonucleotide sequences used for EMSA probes [cIAP2 nuclear factornB (NF-nB) sites 1, 2, and 3] have been described (21).…”

Section: Methodsmentioning

confidence: 99%

Daxx Represses Expression of a Subset of Antiapoptotic Genes Regulated by Nuclear Factor-κB

et al. 2006

Self Cite

View full text Add to dashboard Cite

Daxx is a nuclear protein that localizes to PML oncogenic domains, sensitizes cells to apoptosis, and functions as a transcriptional repressor. We found that Daxx represses the expression of several antiapoptotic genes regulated by nuclear factor-KB, including cIAP2, in human tumor cell lines. Daxx interacts with RelB and inhibits RelB-mediated transcriptional activation of the human cIAP2 gene promoter. Daxx also forms complexes with RelB while bound to its target sites in the cIAP2 promoter, as shown by electrophoretic mobility shift assays and chromatin immunoprecipitation experiments. Using cells from daxxÀ/À mouse embryos, we observed that levels of the corresponding murine c-IAP mRNA and protein are increased in cells lacking Daxx. Conversely, c-IAP mRNA and protein levels were reduced in relBÀ/À cells. Taken together, these observations provide a mechanism that links two previously ascribed functions of Daxx: transcriptional repression and sensitization to apoptosis. (Cancer Res 2006; 66(18): 9026-35)

show abstract

Differences in DNA binding properties between E2F1 and E2F4 specify repression of the Mcl-1 promoter

Cited by 22 publications

References 50 publications

Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions

Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions

Apoptosis Induced by the Kinase Inhibitor BAY 43-9006 in Human Leukemia Cells Involves Down-regulation of Mcl-1 through Inhibition of Translation

Daxx Represses Expression of a Subset of Antiapoptotic Genes Regulated by Nuclear Factor-κB

Contact Info

Product

Resources

About